O'Brien, who grew up in Boston's neighboring Brookline and attended Harvard University across the Charles River in Cambridge, noted his close ties to the city.

"Boston's my hometown. It's where I grew up. It's where my family lives. So I wanted to take a moment to say, that like everyone here, my thoughts and prayers are with the people of Boston and everybody who's been affected by this absolutely senseless act," he said on TBS' "Conan."

"That said, it is our job to do a show and we're gonna try to entertain you the very best we can. Which, given our track record, gives you people a 20 percent chance of having a good show tonight."

"Well, it was a terrible day. Very bad things happened today for no good reason, and our thoughts are with the people of Boston and everyone who is suffering as a result of the bombings at the marathon. It’s a disgusting thing. I don’t understand it. But my job is to make you laugh and so I will try to do that — and, I will probably fail. I’m failing already."

On CBS's "The Late Late Show With Craig Ferguson," the host skipped his normal intro, "It's a great day for America, saying it would be "insensitive at best."

Instead he asked, "Is anyone else sick of this s—? I seem to have to say that too often."

He also noted that people often tell him his job is to make people laugh.

"And I think, 'Well okay, if you want your mind taken off it, you know, watch a cartoon or a video or something. I understand it, it’s perfectly acceptable," he said. "I don’t think it’s a terrible thing to not want to think about it, but I can’t not think about it."

The Scottish-born host also talked about his personal connection to Boston, saying he was invited to speak at Faneuil Hall after he became a U.S. citizen.

"I have some history there. I have family there. When I became an American citizen in 2008, I spoke at Faneuil Hall on July 4, at the invitation of Tommy Menino, who is the mayor of Boston, and one of the more colorful characters in American politics. … I’ve been there for the Fourth of July many times… and every cop in Boston looks like I’m his brother… My first stand up special in America, I shot it in Boston. I used to and I like that town. I’m appalled by this thing and you know, when I watch it on these streets… it’s horrifying.”